Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats.

In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague-Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)-α and interleukin (IL)-1ß, using an enzyme-linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti-IL-1ß and anti-TNF-α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF-α and IL-1ß. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.

An evaluation of the effects on the ovaries of hyperbaric oxygen therapy in a rat model of premature ovarian failure created with cyclophosphamide.

Objective: To evaluate hyperbaric oxygen therapy (HBO) based on ovarian histology, total antioxidant status (TAS), total oxidant status (TOS), and anti-müllerian hormone (AMH), in the ovarian insufiency (POI) model created with cyclophosphamide (CYP). Materials and Methods: The rats were separated into 3 groups of the control group (n=6), the CYP group (n=6), and the CYP+HBO group (n=6). The rats in the CYP group and the CYP+HBO group were injected intraperitoneally with 200 mg/kg CYP on day 1, followed by 8 mg/kg/day for 14 days to create POI. From the 15th day onwards, the rats in the CYP+HBO group were placed in a hyperbaric cabin and exposed to 100% oxygen at 2.4 atm pressure for one h, and were then returned to their cages at the end of the hour. Results: A statistically significant decrease was determined in the primordial and primary follicle counts in the CYP group compared with the control group (p<0.05). In the CYP+HBO group, a statistically significant increase was determined in the primordial and primary follicle counts (p<0.05). The serum AMH levels were seen to be significantly decreased in the CYP group compared with both the control group and the CYP+HBO groups. The HBO was seen to decrease TOS and increase TAS. Conclusion: HBO could be an alternative treatment to minimize the effect of ovarian follicle loss caused by CYP, which is used for treating tumors that commonly occur in young females of reproductive age.

Physical exercise induces structural alterations in the hippocampal astrocytes: exploring the role of BDNF-TrkB signaling.

While it has been known that physical activity can improve cognitive function and protect against neurodegeneration, the underlying mechanisms for these protective effects are yet to be fully elucidated. There is a large body of evidence indicating that physical exercise improves neurogenesis and maintenance of neurons. Yet, its possible effects on glial cells remain poorly understood. Here, we tested whether physical exercise in mice alters the expression of trophic factor-related genes and the status of astrocytes in the dentate gyrus of the hippocampus. In addition to a significant increase in Bdnf mRNA and protein levels, we found that 4 weeks of treadmill and running wheel exercise in mice, led to (1) a significant increase in synaptic load in the dentate gyrus, (2) alterations in astrocytic morphology, and (3) orientation of astrocytic projections towards dentate granule cells. Importantly, these changes were possibly linked to increased TrkB receptor levels in astrocytes. Our study suggests that astrocytes actively respond and could indeed mediate the positive effects of physical exercise on the central nervous system and potentially counter degenerative processes during aging and neurodegenerative disorders.

Anafilaxia tras la administración de amikacina con metabisulfito de sodio a un recién nacido prematuro / Anaphylaxis after administration of amikacin containing sodium metabisulfite in a premature newborn

La anafilaxia es una reacción de hipersensibilidad sistemica y grave, de inicio rápido y potencialmente mortal. En los recién nacidos prematuros, el sistema inmunitario aún no ha madurado y, por lo tanto, tienen menos probabilidades de presentar anafilaxia. La administración de amikacina, que contenía metabisulfito de sodio, a un prematuro de 3 días de vida le indujo anafilaxia casi mortal. Debido a que se sospechaba un caso de anafilaxia, se inició la administración de amikacina en el bebé. Una vez comenzado el tratamiento, se observó una mejoría clínica. Al tercer día de tratamiento con amikacina, el recién nacido tuvo, repentinamente, taquipnea, taquicardia, angioedema y cianosis. Se le diagnosticó anafilaxia y se inició el tratamiento. Una hora después de la mejoría clínica, se produjo una reacción tardía. Inmediatamente, se intubó al recién nacido. La anafilaxia es una emergencia médica; por lo tanto, los médicos deben realizar una evaluación rápida y atenta para detectar esta reacción potencialmente mortal. Incluso después del tratamiento satisfactorio de la anafilaxia, el paciente debe permanecer bajo observación durante 72 horas dada la posibilidad de una reacción bifásica.

Anaphylaxis is a serious systemic hypersensitivity reaction that is rapid in onset and can cause death. Premature newborns, whose immunological system is immature, are less likely to develop anaphylaxis. Administration of amikacin, containing sodium metabisulfite, to a 3-day-old premature newborn, induced a near fatal anaphylaxis. After suspicion of sepsis, the baby was started on amikacin. Clinical improvement was observed after initiation of treatment. On the third day of treatment with amikacin, the newborn suddenly developed tachypnea, tachycardia, angioedema and cyanosis. Anaphylaxis was diagnosed and treated. Latent reaction occurred after one hour of clinical improvement. The baby was intubated immediately. Anaphylaxis is a medical emergency; therefore the clinicians should have a rapid and careful assessment about this potentially fatal reaction. Even after successful treatment of anaphylaxis, the patient should be under observation for 72 hours because of the possibility of a biphasic reaction.

Increased incidence of intermittent hypoxemia in the Ts65Dn mouse model of Down syndrome.

In addition to nervous system, cardiovascular and respiratory systems are primarily affected in Down syndrome (DS). The Ts65Dn mouse model is widely used to recapitulate cognitive dysfunction in DS. While these mice consistently show failure in learning and memory along with functional and structural abnormalities in the hippocampal region, the underlying mechanisms behind cognitive dysfunction remain to be fully elucidated. Convergent evidence implicates chronic episodes of hypoxemia in cognitive dysfunction in people with DS. Using an infra-red detection system to assess oxygen saturation in free-moving mice, we assessed arterial blood oxygenation in both adolescent and adult Ts65Dn mice and found a significant increase in the incidence of hypoxemia in both groups. Notably, the severity of hypoxemia increased during the dark cycle, suggesting a link between hypoxemia and increased motor activity. Postmortem analysis showed significant increase in the expression of mitochondrial Cox4i2, the terminal enzyme of the mitochondrial respiratory chain and oxygen response element. Altogether these data suggest early and chronic occurrence of hypoxemia in the Ts65Dn mouse model of DS, which can contribute to cognitive dysfunction in these mice.

Assessment of dendritic arborization in the dentate gyrus of the hippocampal region in mice.

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity and extent of dendritic arborization correlates well with the synaptic plasticity in these cells. A reliable method for assessment of dendritic arborization is needed to characterize the deleterious effects of neurological disorders on these structures and to determine the effects of therapeutic interventions. However, quantification of these structures has proven to be a formidable task given their complex and dynamic nature. Fortunately, sophisticated imaging techniques can be paired with conventional staining methods to assess the state of dendritic arborization, providing a more reliable and expeditious means of assessment. Below is an example of how these imaging techniques were paired with staining methods to characterize the dendritic arborization in wild type mice. These complementary imaging methods can be used to qualitatively and quantitatively assess dendritic arborization that span a rather wide area within the hippocampal region.

The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed.

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

Does dexmedetomidine provide cardioprotection in coronary artery bypass grafting with cardiopulmonary bypass? A pilot study.

OBJECTIVE: The purpose of this pilot study was to evaluate whether dexmedetomidine has a cardioprotective effect during coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). DESIGN: A prospective, double-blind, randomized controlled trial. SETTING: A university hospital. PARTICIPANTS: Thirty-eight patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomized into 2 groups: dexmedetomidine and placebo groups. In the dexmedetomidine group, dexmedetomidine infusion was started by a loading dose of 0.5 µg/kg/10 min, followed by a continuous infusion of 0.5 µg/kg/h. The placebo group received the same volume of saline. Measurements of central venous pressure, mean pulmonary artery pressure (MPAP) and cardiac index were performed before and after dexmedetomidine loading dose and 2, 24 and 48 hours after CPB. Simultaneously, arterial blood was sampled for CK-MB, cardiac troponin T, and N-terminal probrain natriuretic peptide. MEASUREMENTS AND MAIN RESULTS: CK-MB, cardiac troponin T and N-terminal probrain natriuretic peptide values were elevated in the periods after CPB in both groups (p<0.05) and there were no statistically significant differences between groups. MPAP was decreased in the dexmedetomidine group at the 2nd, 24th and 48th hour after CPB (p<0.001, p<0.001, p = 0.002, respectively). Higher cardiac index values were seen earlier in the dexmedetomidine group than in the placebo group (p< 0.05). CONCLUSIONS: Myocardial damage was not reduced by administration of 0.5 µg/kg loading dose and 0.5 µg/kg/h infusion of dexmedetomidine. However MPAP tended to be lower in the dexmedetomidine group. Large-scale clinical outcome studies are indicated to confirm the effect of dexmedetomidine.